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Expression analysis of the early chemokine response 4 h after in vitro traumatic brain injury

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Abstract

Objective and design

The importance of cytokine- and chemokine-mediated neuroinflammation in the progress of brain injury is becoming increasingly evident. We investigated the early local cytokine and chemokine expression and the development of tissue injury after moderate mechanical hippocampus trauma.

Material or subjects

Mouse organotypic hippocampal slice cultures.

Treatment

Drop-weight trauma in the CA1 region of the hippocampus.

Methods

Staining of necrotic tissue, PCR array and evaluation, real-time PCR, statistical analysis with a two-tailed, independent t test.

Results

At 12 and 24 h after trauma, the tissue injury spread from the primary mechanical lesion to the entire hippocampal formation. A pronounced up-regulation of distinct chemokine transcripts was found 4 h after in vitro traumatic brain injury which preceded the development of the secondary injury.

Conclusions

The enhanced expression of inflammatory genes might contribute to the development of the secondary trauma and could pinpoint future neuroinflammatory and neuroprotective targets for research and treatment.

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References

  1. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99:4–9.

    Article  PubMed  CAS  Google Scholar 

  2. Cross AK, Woodroofe MN. Chemokines induce migration and changes in actin polymerization in adult rat brain microglia and a human fetal microglial cell line in vitro. J Neurosci Res. 1999;55:17–23.

    Article  PubMed  CAS  Google Scholar 

  3. Babcock AA, Kuziel WA, Rivest S, Owens T. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci. 2003;23:7922–30.

    PubMed  CAS  Google Scholar 

  4. Di Pietro V, Amin D, Pernagallo S, Lazzarino G, Tavazzi B, Vagnozzi R, et al. Transcriptomics of traumatic brain injury: gene expression and molecular pathways of different grades of insult in a rat organotypic hippocampal culture model. J Neurotrauma. 2010;27:349–59.

    Article  PubMed  Google Scholar 

  5. Ghirnikar RS, Lee YL, Eng LF. Inflammation in traumatic brain injury: role of cytokines and chemokines. Neurochem Res. 1998;23:329–40.

    Article  PubMed  CAS  Google Scholar 

  6. Ziebell JM, Morganti-Kossmann MC. Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics. 2010;7:22–30.

    Article  PubMed  CAS  Google Scholar 

  7. Ghirnikar RS, Lee YL, He TR, Eng LF. Chemokine expression in rat stab wound brain injury. J Neurosci Res. 1996;46:727–33.

    Article  PubMed  CAS  Google Scholar 

  8. Israelsson C, Bengtsson H, Lobell A, Nilsson LN, Kylberg A, Isaksson M, et al. Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders. Eur J Neurosci. 2010;31:852–63.

    Article  PubMed  Google Scholar 

  9. Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2−/− mice. J Cereb Blood Flow Metab. 2010;30:769–82.

    Article  PubMed  Google Scholar 

  10. Israelsson C, Bengtsson H, Kylberg A, Kullander K, Lewén A, Hillered L, et al. Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury. J Neurotrauma. 2008;25:959–74.

    Article  PubMed  Google Scholar 

  11. Morganti-Kossmann MC, Satgunaseelan L, Bye N, Kossmann T. Modulation of immune response by head injury. Injury. 2007;38:1392–400.

    Article  PubMed  Google Scholar 

  12. Morrison B 3rd, Eberwine JH, Meaney DF, McIntosh TK. Traumatic injury induces differential expression of cell death genes in organotypic brain slice cultures determined by complementary DNA array hybridization. Neuroscience. 2000;96:131–9.

    Article  PubMed  CAS  Google Scholar 

  13. Coburn M, Maze M, Franks NP. The neuroprotective effects of xenon and helium in an in vitro model of traumatic brain injury. Crit Care Med. 2008;36:588–95.

    Article  PubMed  CAS  Google Scholar 

  14. Adamchik Y, Frantseva MV, Weisspapir M, Carlen PL, Perez Velazquez JL. Methods to induce primary and secondary traumatic damage in organotypic hippocampal slice cultures. Brain Res Brain Res Protoc. 2000;5:153–8.

    Article  PubMed  CAS  Google Scholar 

  15. Rossaint J, Rossaint R, Weis J, Fries M, Rex S, Coburn M. Propofol: neuroprotection in an in vitro model of traumatic brain injury. Crit Care. 2009;13:R61.

    Article  PubMed  Google Scholar 

  16. Loetscher PD, Rossaint J, Rossaint R, Weis J, Fries M, Fahlenkamp A, et al. Argon: neuroprotection in in vitro models of cerebral ischemia, traumatic brain injury. Crit Care. 2009;13:R206.

    Article  PubMed  Google Scholar 

  17. Morrison B 3rd, Saatman KE, Meaney DF, McIntosh TK. In vitro central nervous system models of mechanically induced trauma: a review. J Neurotrauma. 1998;15:911–28.

    Article  PubMed  Google Scholar 

  18. ImageJ—Image processing and analysis in Java. http://rsbweb.nih.gov/ij/. Accessed 15 Oct 2010.

  19. SABiosciences web-based analysis tool for PCR arrays. http://pcrdataanalysis.sabiosciences.com/pcr/arrayanalysis.php. Accessed 15 Oct 2010.

  20. Fahlenkamp AV, Coburn M, Haase H, Kipp M, Ryang YM, Rossaint R, et al. Xenon enhances LPS-induced IL-1beta expression in microglia via the extracellular signal-regulated kinase 1/2 pathway. J Mol Neurosci. 2010. doi:10.1007/s12031-010-9432-z.

  21. Lumpkins K, Bochicchio GV, Zagol B, Ulloa K, Simard JM, Schaub S, et al. Plasma levels of the beta chemokine regulated upon activation, normal T cell expressed, and secreted (RANTES) correlate with severe brain injury. J Trauma. 2008;64:358–61.

    Article  PubMed  Google Scholar 

  22. Stefini R, Catenacci E, Piva S, Sozzani S, Valerio A, Bergomi R, et al. Chemokine detection in the cerebral tissue of patients with posttraumatic brain contusions. J Neurosurg. 2008;108:958–62.

    Article  PubMed  CAS  Google Scholar 

  23. Rhodes JK, Sharkey J, Andrews PJ. The temporal expression, cellular localization, and inhibition of the chemokines MIP-2 and MCP-1 after traumatic brain injury in the rat. J Neurotrauma. 2009;26:507–25.

    Article  PubMed  Google Scholar 

  24. Omari KM, Chui R, Dorovini-Zis K. Induction of beta chemokine secretion by human brain microvessel endothelial cells via CD40/CD40L interactions. J Neuroimmunol. 2004;146:203–8.

    Article  PubMed  CAS  Google Scholar 

  25. Szczucinski A, Kalinowska A, Losy J. CXCL11 (interferon-inducible T-cell alpha chemoattractant) and interleukin-18 in relapsing-remitting multiple sclerosis patients treated with methylprednisolone. Eur Neurol. 2007;58:228–32.

    Article  PubMed  CAS  Google Scholar 

  26. Yates CC, Whaley D, Y-Chen A, Kulesekaran P, Hebda PA, Wells A. ELR-negative CXC chemokine CXCL11 (IP-9/I-TAC) facilitates dermal and epidermal maturation during wound repair. Am J Pathol. 2008;173:643–52.

    Article  PubMed  CAS  Google Scholar 

  27. Woller G, Brandt E, Mittelstädt J, Rybakowski C, Petersen F. Platelet factor 4/CXCL4-stimulated human monocytes induce apoptosis in endothelial cells by the release of oxygen radicals. J Leukoc Biol. 2008;83:936–45.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank J. Hoffmann and R. Blaumeiser-Debarry for their excellent technical assistance. The study was supported by two grants allocated to AVF (Forschungsrotation and START, both RWTH Aachen University) and two grants allocated to MK (Hertie-Stiftung; START, RWTH Aachen University).

Conflict of interest

The authors declare that they do not have any conflicts of interest in the context of this work.

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Correspondence to Mark Coburn.

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Responsible Editor: Artur Bauhofer.

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Fahlenkamp, A.V., Coburn, M., Czaplik, M. et al. Expression analysis of the early chemokine response 4 h after in vitro traumatic brain injury. Inflamm. Res. 60, 379–387 (2011). https://doi.org/10.1007/s00011-010-0281-6

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  • DOI: https://doi.org/10.1007/s00011-010-0281-6

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